PROJECT SUMMARY What we know: There are 1.1 million persons living with HIV (PLH) in the US: at least 40% smoke and most want to quit. Almost none are currently accessing smoking cessation interventions designed to meet their specific needs and concerns. PLH who smoke have high rates of nicotine dependence, depression, and loneliness. Lung cancer due to tobacco use is a leading killer of people living with HIV (PLH), accounting for up to 61.5% of mortality. PLH who smoke reduce their life expectancy by 12.3 years on average. The lack of access to proven, effective, and HIV-tailored tobacco cessation services represents a health disparity of the first order. Eighty-one percent of PLH use the Internet and most do so on their own technology?making group-based video- conferencing?accessed through the Internet a promising avenue to deliver smoking cessation treatment. Although cessation programs are widely offered to the general public, there are no evidence-based programs available specifically for PLH and none found effective long-term for this population; no programs provide group- based video-conferencing (VG for video-groups); and no PLH-specific programs provide smoking cessation booster sessions. What we will do: In this rigorous trial, the efficacy of a PLH-specific cessation program (PSF- VG), guided by the Social Cognitive Theory, will be compared to an attention matched control condition (AMC; prevention with positives) in a randomized control trial. Participants will be N=482 PLH smokers recruited from Florida who are motivated to quit within the next 30 days. All participants will be offered nicotine replacement therapy and brief cessation counseling in addition to an 8-session intervention with booster sessions (PSF-VG or AMC). The primary outcome will be biochemically confirmed 7-day point prevalence abstinence at 12 months follow-up, although 30-day point prevalence abstinence and sustained abstinence (continuous abstinence post- quit day after a 2-week grace period) will be assessed, as well. We will also determine the cost per additional quit, an important cost-effectiveness measure for smoking cessation. We will examine model-driven hypotheses about the mediators of treatment outcome (e.g., knowledge, motivation to quit, self-efficacy), and explore effects on CD4 count and virologic suppression. Implications: 1) This trial will represent one of the most rigorous trials of tobacco cessation among PLH to date, given the AMC and 360-day follow-up period. 2) Establishing the long- term efficacy of a VG smoking cessation program for PLH, which reaches PLH ?where they are,? will represent an enormous advance in the fight against tobacco use in PLH and provide a clearer understanding of the role of targeted, ehealth health interventions in comprehensive HIV care. 3) Determining the costs associated with this program will be critical for making real world implementation decisions. 4) Establishing effect mediators will help identify to what extent PSF-VG is working as intended and help build the mechanistic science of HIV smoking cessation. 5) Examining changes in CD4 and viral load will add to our understanding about how smoking cessation confers benefits for health in PLH. Thus, this study will likely have a high impact on the field.